Abstract
Treatment of the human promyelocytic leukemia cell line HL-60 with antisense oligodeoxynucleotides to UDP-N-acetylgalactosamine:beta-1,4-N-acetylgalactosaminyl-transferase (GM2-synthase; EC 2.4.1.92) and CMP-sialic acid:alpha-2,8-sialyltransferase (GD3-synthase; EC 2.4.99.8) sequences effectively down-regulated the synthesis of more complex gangliosides in the ganglioside synthetic pathways after GM3, resulting in a remarkable increase in endogenous GM3 with concomitant decreases in more complex gangliosides. The treated cells underwent monocytic differentiation as judged by morphological changes, adherent ability, and nitroblue tetrazolium staining. These data provide evidence that the increased endogenous ganglioside GM3 may play an important role in regulating cellular differentiation and that the antisense DNA technique proves to be a powerful tool in manipulating glycolipid synthesis in the cell.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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Carbohydrate Sequence
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Cell Differentiation / drug effects
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Cell Division
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Down-Regulation
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Gene Expression Regulation, Leukemic*
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Glycolipids / biosynthesis*
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Glycosphingolipids / analysis
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Glycosyltransferases / drug effects*
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Humans
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Leukemia, Promyelocytic, Acute / enzymology
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Leukemia, Promyelocytic, Acute / genetics*
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Leukemia, Promyelocytic, Acute / metabolism
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Molecular Sequence Data
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N-Acetylgalactosaminyltransferases / drug effects
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Oligonucleotides, Antisense / pharmacology*
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Polypeptide N-acetylgalactosaminyltransferase
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Sialyltransferases / drug effects
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Tumor Cells, Cultured
Substances
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Glycolipids
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Glycosphingolipids
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Oligonucleotides, Antisense
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Glycosyltransferases
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N-Acetylgalactosaminyltransferases
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(N-acetylneuraminyl)-galactosylglucosylceramide N-acetylgalactosaminyltransferase
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Sialyltransferases
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alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
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haematoside synthetase